2026 Pediatric Lupus Research Grant Awardee

Holly Wobma, MD, Ph.D.

Institution: Boston Children’s Hospital 

Project Title: Armored CAR-Treg Therapy to Induce Immune Tolerance in pediatric SLE

Project Summary: Pediatric-onset systemic lupus erythematosus (pSLE) is a chronic autoimmune disease that often causes severe illness and begins during critical periods of childhood development. Current treatments suppress the immune system but do not cure the disease, and long-term use can lead to serious side effects. Achieving lasting, drug-free remission early in life could greatly improve long-term health and quality of life for children with pSLE.

Recent advances using immune cells with engineered receptors, called chimeric antigen receptor (CAR)-T cells, suggest that long-lasting remission in lupus may be possible by eliminating disease-driving immune cells. However, these therapies require chemotherapy before infusion and carry risks of infection and harmful inflammation. These risks are especially concerning for children and may limit use in pediatric autoimmune disease.

Regulatory T cells (Tregs) are immune cells that naturally calm inflammation and help maintain immune balance. When engineered with CARs, Tregs can become active at sites of disease and suppress autoimmune inflammation without destroying other immune cells. CAR-Treg therapies therefore offer a promising and potentially safer approach for treating pSLE.

This project aims to improve how CAR-Tregs function in the inflammatory environments seen in lupus. The same inflammatory signals, called cytokines, that drive lupus may also weaken Tregs and limit their effectiveness. We propose to engineer CAR-Tregs with an added feature that allows them to locally capture and remove specific inflammatory cytokines, creating cytokine “nets” that protect Tregs from inflammatory stress while reducing harmful signals to nearby immune cells.

This work will improve understanding of how inflammation disrupts Treg immune regulation in lupus and test whether cytokine-net-enhanced CAR-Tregs can better restore immune balance. The long-term goal is a safer cellular therapy for durable, drug-free remission for pSLE.